Biological aortic valve replacement began in approximately 1962. This early work was initiated because artificial heart valve replacements were plagued with mechanical breakdown and the requirement to anticoagulate the patient.
Biological valves, usually porcine or bovine origin, had the overall advantage of identical design and structure to that of the valve being replaced. Today, approximately 18,000 out of 36,000 total valves replaced in United States each year are tissue valves. Virtually all of the 18,000 biological valves are of bovine or porcine origin, glutaraldehyde-fixed and mounted on a mechanical stent. However, these types of biological valves are non-living. Consequently, time and biological reaction to the non living material work to degrade the tissue until its eventual malfunction.
Because of the inherent problems in using non-living heart valves of animal origin, researchers have begun using human allograft heart valves for replacement of defective heart valves. The human allograft valve is useful either by itself or in association with its conduit, i.e., the aorta with the aortic valve or the pulmonary valve with the pulmonary artery, for use as a crucial constituent in congenital heart repair. Pulmonary outflow tract reconstruction using aortic and pulmonary valve conduits are used routinely for complex tetralogy of fallot, pulmonary atresia, truncus arteriosus and complex transposition of the great arteries. Heretofore, for these congenital defects which occur in eight out of every one thousand births, artificial valves were used in conjunction with artificial vascular conduits. These reconstructive procedures are subject to the same deleterious clinic effects of calcific degeneration and thrombo embolic occurrences as with a non-allograft valve used alone.
Investigators have generally agree that fresh tissue gives improved performance over old or dead tissue, and viable human tissue exceeds the useful performance of the bovine/porcine xenograft valves. However, viable tissue remains alive for only short periods of time. The fibroblast cells, which are the major constituent of the valve leaflet and are the cells which are most important for proper valve functioning and longevity, will remain viable for, at most, two or three days in a life sustaining media. Storage for two or three days is impractical for all but a few of the valve recipients because the valve size of the donor tissue is unlikely to be the correct size for the waiting recipient. Consequently, much of the tissue can not be used for valve replacement because of a severe loss of cell viability with time. Additionally, preservation time becomes increasingly more important in light of the fact that increasing evidence exits for improved tissue performance if the donor and recipient are of the same ABO blood group.
A number of investigators have devised various methods to extend storage life of heart valves. Prior art techniques, such as freeze drying, glutaraldehyde fixation, and mechanical freezing, combined with sterilization techniques of irradiation and antibiotics generally lead to early failure of the tissue.
The storage of cells and tissues became possible after the discovery in 1949, by Polge, Smith, and Parks, that glycerol could be used to protect cells from injury due to freezing. With the advent of low temperature biology, workers in medical and biological fields have been seeking better ways to maintain the viability of frozen donor cells or tissues.
Several methods for freezing cells and cell aggregates have been reported. U.S. Pat. No. 3,303,662 discloses a process for cell preservation which utilizes a cryoprotectant in the freezing process. U.S. Pat. No. 4,423,600 discloses a method for preservation of living organic tissue by freezing which involves lowering atmospheric pressure surrounding the tissue before freezing.
Several attempts have been made to freeze heart valves to ultra-cold temperatures. (e.g., Van der Kemp, et al., Journal of Surgical Research, Vol. 30., 47-56, 1981). However, even with the realization that enzymatic degradation of the tissue during long-term storage is minimal at the ultra-cold temperatures of liquid nitrogen, a multitude of problems have been encountered in the implementation of this technology. What is needed, is a method of freezing heart valves to ultra-cold temperatures that will maintain maximum viability of individual cells within the tissue with minimal tissue degradation. The method should allow long term storage of the biological tissue.